Personalized oncogenomic analysis of metastatic squamous cell carcinoma of the anus: Utilizing whole-genome sequencing to guide clinical decision-making.
Notice bibliographique
Résumé
11 Background: Metastatic squamous cell carcinoma of the anus (SCCA) is associated with significant morbidity and mortality. Due to its relative rarity, there is limited evidence to support systemic therapy regimens informed by genomic data. This study aims to utilize whole-genome and transcriptome sequencing to enhance the understanding of the genetic alterations driving metastatic SCCA and to identify potentially actionable therapeutic targets. Methods: This report examines nine cases of metastatic SCCA in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Comprehensive genomic profiling, including whole-genome and transcriptome analysis (WGTA) was conducted on fresh tumor biopsy or formalin fixed paraffin embedded (FFPE) tissue. Tumor genomic alterations were analyzed in detail including: SNVs, indels, copy number alterations, structural variants, mutation signatures, viral presence, tumor mutation burden (TMB), expression outliers, and immune cell scores. The somatic alterations were integrated with existing knowledge of drug-target interactions to identify actionable therapeutic targets. Results: Of the nine patients, eight were found to be HPV-positive, with one exhibiting high tumor mutational burden (TMB>10mut/Mb). Mutation signatures included seven cases with AID/APOBEC signatures (commonly seen with HPV), and one case with an ID2 DNA replication slippage signature. The PI3K/AKT/mTOR pathway was the most commonly affected signaling pathway (n=4), followed by FGFR amplification and overexpression (n=3), and RAS/RAF alterations ( BRAF mutation and KRAS overexpression, n=2). EGFR amplification was identified in two cases, one of which also exhibited EGFR overexpression. Additionally, FBXW7 mutations were present in two cases. Immunotherapy was recommended for all nine patients: eight based on HPV positivity, either alone or in combination with other alterations, such as high TMB, SWI/SNF complex alterations, and presence of immune infiltrating cells, and the remaining case based on a SWI/SNF complex mutation. Only two patients ultimately received immunotherapy, both of whom derived clinical benefit. One patient, treated with atezolizumab as part of the phase II CAPTIV-8 trial (NCT04273061), demonstrated progression-free survival (PFS) of 10 months (ongoing), while the other, treated with nivolumab, achieved a PFS of 6 months. Conclusions: Genomic analysis using WGTA supported the recommendation of immunotherapy for all patients in this cohort. Although only two patients received immunotherapy, both experienced clinical benefit, underscoring the potential of personalized genomic-guided treatment in metastatic SCCA.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,008 | 0,015 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,004 | 0,003 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».